Glutamate-mediated astrocyte–neuron signalling

Abstract

Neurotransmitter released from neurons is known to signal to neighbouring neurons and glia. Here we demonstrate an additional signalling pathway in which glutamate is released from astrocytes and causes an NMDA (N-methyl-D-aspartate) receptor-mediated increase in neuronal calcium. Internal calcium was elevated and glutamate release stimulated by application of the neuroligand bradykinin to cultured astrocytes. Elevation of astrocyte internal calcium was also sufficient to induce glutamate release. To determine whether this released glutamate signals to neurons, we studied astrocyte-neuron co-cultures. Bradykinin significantly increased calcium levels in neurons co-cultured with astrocytes, but not in solitary neurons. The glutamate receptor antagonists D-2-amino-5-phosphonopentanoic acid and D-glutamylglycine prevented bradykinin-induced neuronal calcium elevation. When single astrocytes were directly stimulated to increase internal calcium and release glutamate, calcium levels of adjacent neurons were increased; this increase could be blocked by D-glutamylglycine. Thus, astrocytes regulate neuronal calcium levels through the calcium-dependent release of glutamate.

Supportive or information-processing functions of the mature protoplasmic astrocyte in the mammalian CNS? A critical appraisal

“…The original observations, which were interpreted as vesicular release, were made with primary astrocyte cultures (Parpura et al, 1994;Araque et al, 2000;Pasti et al, 2001;Montana et al, 2004).…”

Integrated Brain Circuits: Neuron-Astrocyte Interaction in Sleep-Related Rhythmogenesis

“…In 1994, Parpura and colleagues conducted a set of experiments making an intriguing discovery: cultured astrocytes release glutamate, which leads to Ca 2+ elevation of nearby neurons[70]. Later studies demonstrated that this process can be observed in acute brain slices[71,72,73,74,75,76,77,78,79] and in vivo [80].…”

Polyketide stereotetrads in natural products

“…11 The remaining steps for the C 9 -C 19 fragment of Calyculin C are shown in Scheme 5. 12 The lactone aldehyde 43 was first allowed to react with a chiral crotyl borane reagent 44 yielding 2 , CSA, acetone; f (n-Bu) 4 NF, THF; g Pyr?SO 3 , Et 3 N, DMSO; h K 2 CO 3 , MeOH. a 6 : 1 diastereomeric mixture of two anti homoallylic alcohols.…”

“…7) was isolated from Streptomyces nodosus in 1956 and its stereochemical structure was resolved 15 years later by X-ray analysis. 4 , (2) K. C. Nicolaou and his group were the first ones to develop a total synthesis for amphotericin B and amphoteronolide B. 17 In their retrosynthetic analysis the syn, anti, anti stereotetrad (boxed in Fig.…”

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